As an important fine chemical, phenylacetic acid is used widely in the industries of pesticide, pharmaceuticals, perfume or the like.
In the pharmaceuticals industry, phenylacetic acid is converted to sodium salt, potassium salt or other derivatives of phenylacetic acid, such as low toxic precursor phenylacetyl ethanolamine as the precursor of fermentation for producing penicillin to prepare penicillin G. In addition, phenylacetic acid can be converted by chlorination under various conditions to intermediates such as α-chlorophenylacetic acid, p-chlorophenylacetic acid, o-chlorophenylacetic acid, trichlorophenylacetic acid and phenylacetyl chloride etc. p-Chlorophenylacetic acid can be used for producing Azeptin, a medicine developed by Asta-Werke AG, Germany for treating diseases such as bronchial asthma, allergic rhinitis and the like. o-Chlorophenylacetic acid can be used for producing diclofenac sodium, which is a potent anti-inflammatory analgesic medicine. Testosterone phenylacetate, a gonadal hormone, can be produced by reacting phenylacetyl chloride with testosterone. Phenylacetyl chloride can also be used for the synthesis of lorcamide hydrochloride (Lopantrol), which is a novel anti ventricular arrhythmia medicine and has local anesthetic effect. Nitrification of phenylacetic acid under various conditions can produce p-nitrophenylacetic acid, o-nitrophenylacetic acid, m-nitrophenylacetic acid and 2,4-dinitrophenylacetic acid, respectively. p-Nitrophenylacetic acid can be used to produce analgesic and antipyretic medicines such as biphenylacetic acid, pirprofen, ketoprofen, etc. and novel antirheumatic medicine Acrarit with an immunoregulatory effect. 2,4-Dinitrophenylacetic acid can be used in the synthesis of p-aminosalicylic acid, and the latter is a key raw material in the synthesis of the antitubercular medicine sodium para-aminosalicylate PAS-Na. By using phenylacetic acid, phthalic anhydride as raw materials, o-phenylethyl benzene carboxylic acid can be produced by condensation, hydrolysis, hydrogenation, and then neutralization with an acid, and an intermediate benzocycloheptadienone can be further produced, which is a key raw material in the synthesis of tricyclic antidepressant amitriptyline, nortriptyline and antihistaminic agent cyproheptadine. Dibazol, which is used for treating diseases such as mild hypertension and hypertension complicating with coronary heart disease, etc. can be produced by condensation of phenylacetic acid and o-phenylenediamine. Phenylacetic acid also can be used to synthesize benzodiazepine-based derivatives such as estazolam, diazepam, nitrazepam, fludiazapam and the like, which have been developed just since 1980s, and have better therapeutic effect and higher reliability than barbiturates, and are anti-anxiety drugs which are developed relatively fast, the most widely used and have excellent therapeutic effects. In addition, phenylacetic acid is also widely used in preparation and synthesis of antiepileptic drugs, antidepressant, cardiovascular drugs and antirheumatic drugs.
In the pesticide industry, it is mainly used in the production of insecticides, bactericides, herbicides, rodenticides and the like. For example, the halogenated derivatives of phenylacetic acid, such as α-chlorophenylacetic acid or α-bromophenylacetic acid, the esterified products thereof can be used to synthesize ethyl phenthoate, a non-systemic organophosphorus pesticide and acaricide, which is especially potent for killing coccid. 2,4,6-Trichlorophenylacetic acid is usually prepared in the form of sodium salt aqueous solution commonly known as “fenac”, used as a herbicide for the plantations of maize, sugarcane or the like. Phenylacetyl chloride can be used to synthesize N-acylalanine-based systemic bactericide, i.e. benalaxyl, which has good properties, and three characters of low botanic toxicity index, special mechanism of action, and high activity. Phenylacetyl chloride is also widely used as a raw material for a potent rodenticide, i.e. anticoagulant rodenticide, which essentially comprises commercially available products such as Talon, Ratak, Starm, LM-2219 and the like. A phenylacetic acid derivative, phenylacetone can be used to synthesize agropesticide, and it can further be used to produce indanedione-based rodenticides, such as diphacinone sodium salt, chlorophacinone and the like. A derivative of phenylacetic acid, o-nitrophenylacetic acid, can be used to synthesize good herbicides.
In the perfume industry, various phenylacetate ester compounds can be synthesized from phenylacetic acid by esterification, which are used as perfume fixative and modifier in the perfume (essence) industry, and widely used in the industries of soap, detergent, cleanser, cosmetics, tobacco, food, etc.
Phenylacetic acid is a very important fine chemical raw material and many products can be derived therefrom. In recent years, the demand for phenylacetic acid further increases, along with the developments of industries of pharmaceuticals, pesticide, and perfume.
At present, there are dozens of routes for the synthesis of phenylacetic acid. The followings are commonly used: sodium cyanide process, styrene process, acetophenone process and benzyl halide carbonylation process.
Currently, the sodium cyanide process is the most widely used process in China. Although this process is simple and the condition is mild, and can co-produce benzyl cyanide, this process has a higher cost, and the raw material sodium cyanide is highly toxic, with poor safety and tremendous influence on the environment, resulting in severe pollution and requiring higher cost to clean the environment, and therefore the application of this process is limited.PhCH2Cl+NaCN→PhCH2CN+NaClPhCH2CN+NaOH+H2O→PhCH2COONa+NH3 PhCH2COONa+H2SO4→PhCH2COOH+Na2SO4 
Currently the carbonylation process of benzyl halide is more popular. This process selects benzyl halide and carbon monoxide as raw materials, and obtains phenylacetic acid by a transition metal catalyzed process.PhCH2Cl+2NaOH+CO→PhCH2COONa+NaCl+H2OPhCH2COONa+HCl→PhCH2COOH+NaCl
This process was first industrially developed by Dynamit Nobel AG, Germany, and then in other countries some industrial plants were set up. In China, the research in this process began in the late 1980s, and since 1990s some manufacturing plants were set up. Because the raw materials in this process are easy to obtain and the cost is relative low, it was widely investigated (CN1039241, CN1054584, CN1093355, CN1110677, CN1109871, CN1284406, CN85100362, CN101716523A, CN101816952A, etc.). After many years of development, the process is already a mature process and can be performed at lower pressure and lower temperature. However, in this process benzyl halide is used as a raw material, and a large amount of acidic waste is produced in the reaction, therefore plenty of base is needed, which results in a low economical efficiency and more influences on the environment, thus limits the application of the process, and the cost of production is relative high.
Accordingly, it is especially important to use some environmental friendly materials and to provide an environmental friendly process for producing phenylacetic acid based compound.